Raised CSF phospho-tau concentrations in variant Creutzfeldt-Jakob disease: diagnostic and pathological implications

Objective: To investigate whether phosphorylated tau protein (tau-pT181) is increased in variant Creutzfeldt - Jakob disease (vCJD) and if the tau-pT181/tau protein ratio is useful for distinguishing between patients with and without CJD. Methods: CSF tau protein and tau-pT181 were measured in 50 patients with sporadic CJD (sCJD), 51 patients with vCJD, 46 sCJD controls, and 37 vCJD controls, using Innotest hTau and Innotest P-Thr181, Innogenetics. Results: Concentrations of CSF tau protein were increased in sCJD ( 5120 v 367 pg/ml in controls, p< 0.001) and vCJD ( 952 v 106 pg/ml, p< 0.001); tau- pT181 was also raised in sCJD ( 61 v 35 pg/ml in controls, p = 0.002) and vCJD ( 114 v 33 pg/ml, p< 0.001). Median concentrations of tau- pT181 were higher in vCJD than in sCJD ( p, 0.001). The taupT181/ tau protein ratio was lower than in controls in both sCJD ( 12 v 128 ( p, 0.001)) and vCJD ( 119 v 279 ( p, 0.001)). Mean tau- pT181/tau protein ratio was 10-fold higher in vCJD than in sCJD. Raised CSF tau protein had the highest efficiency for distinguishing sCJD and vCJD from controls. Conclusions: CSF tau- pT181 concentrations are raised in vCJD and are higher than in sCJD. Measurement of CSF taupT181/ tau protein ratio does not improve the diagnostic efficiency of CSF tau protein alone for either vCJD or sCJD. The higher concentration of CSF tau- pT181 found in vCJD suggests that unexplained pathogenic factors influence the phosphorylation of tau protein in vCJD patients.